Authors: Mark M. Muenchrath, S. Omar Gilani, Sandy Christiansen, Scott P. Landreth, L.P. Ricelli
Categories: Case Report, Brachial plexus, Cancer, Case report, Neuropathic pain, Peripheral nerve stimulator
Source: Interventional Pain Medicine
Authors: Mark M. Muenchrath, S. Omar Gilani, Sandy Christiansen, Scott P. Landreth, L.P. Ricelli
Chronic neuropathic pain has a prevalence between 7 and 11% of the population. Management typically involves pharmacologic agents, however, a high number needed to treat (NNT) and undesirable side effects limit their utility. Neuromodulation techniques, such as peripheral nerve (PNS) and spinal cord stimulators (SCS), have been utilized successfully in the treatment of chronic neuropathic pain syndromes. To date, there is limited evidence supporting use of PNS for cancer-related neuropathic pain.
An 83 year old male presented to the outpatient pain clinic after experiencing worsening pain related to brachial plexus invasion from a left anterior chest wall metastatic lesion from a primary lung cancer. His treatment had included a left upper lobectomy followed by radiation and an initial round of chemotherapy. The chest wall metastatic lesion was unable to be resected. After subsequent tumor progression, the mass caused a worsening dull, achy pain in his left shoulder radiating down his left arm. A PNS system was implanted targeting the inferior trunk of the brachial plexus. The patient's pain score decreased after activation of the device and he was able to rely solely on the stimulator for pain management until his eventual death.
This patient experienced a substantial reduction in pain and improvement in his quality of life through his eventual death suggesting PNS as a viable palliative pain option for neuropathic pain due to tumor invasion.
Chronic neuropathic pain is widespread with a prevalence between 7% and 11% of the total population [1]. For cancer patients, 62% of patients experience neuropathic pain due to direct tumor involvement versus 25% due to chemotherapy, radiation, or surgery [2].
Management typically involves pharmacologic agents, however these may not produce sustained improvement and can lead to undesirable side effects. Neuromodulation techniques in the form of peripheral nerve (PNS) and spinal cord stimulators (SCS) have been utilized successfully in the treatment of chronic neuropathic pain syndromes, including complex regional pain syndrome (CRPS) type I and II, post laminectomy pain, peripheral neuropathy, post-traumatic/surgical neuralgias, post-amputation pain, and post-herpetic neuralgia. Implementing neuromodulation in the cancer-related pain population requires consideration of location of the cancer, cancer treatment, co-morbidities, cost, accessibility of interventional targets, and risk of complications.
This case demonstrates the novel use of peripheral nerve stimulation (PNS) to treat neuropathic pain caused by a metastatic lung cancer lesion invading into the brachial plexus. An 83 year old male presented to the outpatient pain clinic with worsening left upper extremity pain refractory to medication therapy in the setting of treatment resistant lung cancer. The patient was primarily interested in approaches to his pain that would improve his quality of life; neuropathic pain medications, though helpful, were causing significant side effects. A literature review found case reports as well as randomized control trials demonstrating the use of PNS to treat brachial plexopathies caused by trauma or surgery, however published literature on the use of PNS for cancer related brachial plexopathies is limited. This patient experienced a substantial reduction in pain and improvement in his quality of life through his eventual death suggesting PNS as a viable palliative pain option for neuropathic pain due to tumor invasion.
An 83 year old male presented to the outpatient pain clinic after experiencing worsening pain related to brachial plexus invasion from a primary lung cancer. His initial symptoms, prior to his lung cancer diagnosis, included intermittent left-sided chest pain, 20 pounds of weight loss, and voice changes. He was found to have a left upper lobe lung mass and a left anterior chest wall metastatic lesion at the time of diagnosis. He ultimately underwent a left upper lobectomy with mediastinal lymph node dissection with pathology revealing an invasive squamous cell carcinoma. The chest wall lesion was unable to be resected at the time of surgery. After this procedure, he continued treatment with Durvalumab and localized radiation, however the residual left anterior chest wall mass was unresponsive to treatment. Upon further consideration the patient and his family decided to defer treatment with a platinum-based chemotherapy agent due to his advanced age and risk of severe peripheral neuropathy, which would subsequently interfere with his independent, active lifestyle. He elected for symptom management for the remainder of his life.
In the absence of treatment and subsequent tumor progression, the mass caused a worsening dull, achy pain in his left shoulder radiating down his posterior arm, medial forearm, and fourth and fifth digits. The patient described this radiating pain as a burning pain, particularly with movement. His pain medication regimen included oxycodone and gabapentin but despite the medications, the pain averaged 6/10 in severity. Sedation limited the ability of his palliative care provider to increase the medication dose. Acetaminophen had also been tried but caused transaminitis and was eventually discontinued. The patient and his family were interested in interventional pain treatment options to improve his pain with the goal of minimizing his reliance on neuropathic pain medications that were causing side effects.
Surveillance CT scans following surgery showed a left anterior chest wall soft tissue mass measuring 4.2 cm by 2.4 cm. In preparation for peripheral nerve stimulator placement, an MRI of the brachial plexus was obtained and showed the left axillary anterolateral chest wall mass (Fig. 1 and Fig. 2). The mass directly invaded the left second rib, lung pleura, and all cords and divisions of the brachial plexus. Despite the imaging findings, this patient's symptoms and physical exam findings were limited to the C8 and T1 dermatomes and myotomes (see Fig. 3).Fig. 1Brachial plexus MRI demonstrating tumor invasion – post-contrast axillary view.Fig. 1Fig. 2Brachial plexus MRI demonstrating tumor invasion – post-contrast sagittal view.Fig. 2
Both spinal cord and peripheral nerve stimulation (SCS and PNS) were discussed in detail with the patient as therapeutic options for his neuropathic pain. After the discussion, the patient and his family recognized the greater body of evidence for spinal cord stimulators in treating neuropathic pain but ultimately chose to proceed with peripheral nerve stimulator implantation. From their perspective, the PNS implant procedure was less invasive and potentially required fewer doctor visits overall, which they valued as they lived several hours from the pain clinic (see Fig. 4).Fig. 3PET Demonstrating Tumor invasion.Fig. 3Fig. 4Ultrasound peripheral nerve stimulator placement targeting the brachial plexus inferior trunk.Fig. 4
The physician and patient elected to use a Bioness Stimrouter device, which utilizes an external pulse transmitter to deliver impulses to tunneled stimulator lead. On the day of the procedure, a linear ultrasound probe was used for target visualization during placement. The patient was placed in the lateral decubitus position. Scanning craniocaudally, the left clavicle and the left subclavian vein were visualized before tracing the brachial plexus supraclavicularly proximal to the cancer lesion.
A 21-gauge 50 mm needle was advanced under ultrasound guidance to target the inferior trunk of the brachial plexus supraclavicularly. A stimulator probe was inserted through the needle and the position of the probe was adjusted until the patient felt sensory stimulation in his area of pain at 50 Hz.
Following stimulation, the needle was removed and an introducer needle was placed over the stimulator probe. The stimulator probe was removed and the peripheral nerve stimulator lead was inserted into the introducer needle. Once in position, stimulation was checked again for reproduction of the patient's typical pain. Following confirmation of stimulation, the introducer needle was removed and the proximal portion of the lead was tunneled subcutaneously over the trapezius muscle in the area between the neck and the shoulder dorsally. On the day of the procedure, the patient's pain score decreased from 8/10 before PNS placement to 0/10 after placement and activation of the device.
During the initial post-procedure visit on POD#2, the patient reported some incisional left shoulder pain and 60% relief of his typical neuropathic pain. Over the following weeks, due to the pain relief from the stimulator, the patient was able to titrate off all neuropathic pain medications and relied solely on the stimulator for pain management until his eventual death two months after the stimulator was placed.
The use of neuromodulation techniques in the form of peripheral nerve and spinal cord stimulation devices have been gaining support in recent decades as targeted, safe, nondestructive, and reversible means of managing chronic pain. A proposed mechanism of action was provided by Melzack and Wall's gate control theory developed in 1965 [3]. Since this time, the mechanisms of neuropathic pain transmission and how neuromodulation reduces neuropathic pain has expanded beyond gate control theory. Both spinal cord stimulation and peripheral nerve stimulation rely on similar mechanisms - mediating pain through inhibition of inflammatory neuropeptide release, synaptic depression, glial cell activation, and supraspinal descending modulation - but the exact mechanism and mechanism differences between PNS and SCS are still unknown [4,5].
Spinal cord stimulation is the most established modality of neuromodulation with clinical trials supporting its use as a modality for treating several neuropathic pain syndromes including failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) [6,7].
Similarly, there is evidence supporting the use of PNS. Early PNS use targeted neuropathic craniofacial pain [9] with more recent use for brachial plexopathies, peripheral nerve injuries, complex regional pain syndrome, phantom limb pain after amputation, and fibromyalgia [[10], [11], [12]].
Kim et al. reported two cases in which PNS was used successfully to treat motor vehicle accident induced brachial plexus injuries [13].
A case series by Bouche et al. reports the successful use of PNS in 10 patients with upper extremity neuropathic pain because of direct nerve injuries distal to the brachial plexus. In these patients, the leads were implanted between the scalene muscles at the nerve roots or at the suprascapular nerve. At one year follow up appointments, eight patients reported a mean pain relief of 68% and had reduced analgesic requirements. The authors hypothesized that, in comparison to more distal implants, targeting the proximal brachial plexus in this study made lead implantation easier via ultrasound guidance, and the permanent implant more comfortable for the patient [14].
In a randomized controlled trial, Deer et al. evaluated the efficacy of a PNS device with an internalized lead and an external pulse transmitter in treating upper extremity, lower extremity, and truncal pain [15]. They implanted the PNS leads in post-traumatic or post-surgical neuropathic pain patients then randomized patients to neuromodulation or to no neuromodulation with a later option to turn on neuromodulation. They found a 27.2% mean improvement in pain scores at three months after PNS implantation in patients with active neuromodulation compared to 2.3% improvement in the control group. The treatment group also displayed significant improvement in quality of life and satisfaction scores. One third of the control group who chose to activated neuromodulation also showed a pain score improvement of greater than 30% after three months of treatment [15]. This study has been the only randomized controlled trial assessing PNS in the treatment of post-traumatic and post-surgical chronic neuropathic pain but does not specifically evaluate pain that is brachial plexus in origin and does not evaluate cancer related pain.
With regards to oncologic pain, most of the evidence for neuromodulation supports the use of spinal cord stimulation. SCS has successfully treated cancer associated pain caused by tumor invasion, chemotherapy related neuropathy, surgery for tumor resection, and radiation therapy [16]. Mirpuri et al. and Hutson et al. described multiple patients with pain due to bone metastases, which was refractory to conventional medical management, successfully treated with SCS placement reducing pain while reducing opioid requirements and improving function [17,18]. Other cases have shown success using SCS to treat radiation caused neuropathic pain both from nerve entrapment after radiation and from transverse myelitis [19,20].
Evidence for PNS use in oncologic pain is limited. Mainkar et al. completed a pilot case series examining a temporary 60-day PNS lead implant in 12 oncology patients with various etiologies of neuropathic pain including radiation induced, direct tumor invasion into neuronal tissue, and post-surgical pain. Seven of the 12 patients experienced greater than 50% relief of pain while the stimulator was in place, and some experienced continued pain relief after explant. Of note, one of the patients in this series had a metastatic lesion encasing the brachial plexus and received PNS implantation in the supraclavicular brachial plexus similar to the featured patient. The patient's pain improved from 8 out of 10 to 2 out of 10 during stimulation and remained at 2 out of 10 after the stimulator was explanted as it reached the 60-day limit [21].
These successful cases indicate that neuromodulation is an appropriate treatment modality for cancer related neuropathic pain. Evaluation of the National Anesthesia Clinical Outcomes Registry (NACOR) has shown reduced time for PNS placement averaging 88 minutes compared to 98 minutes for SCS placement [22]. No study has yet compared the post-operative clinical demands of SCS versus PNS, including number of post-operative visits, reprogramming frequency or explant rate. This information would be valuable in guiding the clinical decision. The explant rate for permanent PNS implants for CRPS was determined to be 19% in a single center retrospective review of 165 patients [23]. The most common reason for explant was lack of efficacy or loss of therapeutic effect which accounted for 50% of cases with a median time to explant of 40 months. The explant and therapeutic failure rates for SCS appear to be similar. Retrospective reviews examining dorsal column stimulation for various indications have found explant rates of 23.9% [24] and 30% [25], with loss of therapeutic effect accounting for 39% [24] and 28% [25] of all explants.
Cancer related neuropathic pain due to direct tumor invasion has been effectively treated with SCS. As discussed above, there is limited data regarding the use of PNS in this cohort of patients. Our patient's pain was in the C8 and T1 dermatomal distribution and the location of the tumor encircling the cords and divisions of the brachial plexus enabled us to access the roots and trunks proximal to the lesion. The inferior trunk of the brachial plexus was chosen as the target for PNS as it is formed by the convergence of the ventral rami of the C8 and T1 nerve roots which corresponded to the patient's pain distribution. It therefore provided the most focused and efficient neurostimulation without stimulating asymptomatic regions of the brachial plexus. However, if the clinical symptoms expanded due to the growing cancer lesion, the parameters of stimulation could have been altered to cover a broader region of pain.
Electrodiagnostic studies like electromyography and nerve conduction studies can determine the location, extent, and type of peripheral nerve injury. They may have some utility in the decision-making process if the etiology of neuropathic pain was unclear [26]. However, the character and dermatomal distribution of the patient's symptoms correlated well with the known mass on imaging. With the patient's palliative goals of care, the decision was made to forego electrodiagnostic studies which would not have changed management. Further, these tests do have limitations of providing varying results based on timing and extent of injury, and are less reliable in advanced age [26].
Within the oncologic population, MRIs are used to monitor disease progression and therapeutic planning as they demonstrate superior soft tissue resolution to other imaging modalities. Neuromodulation devices are either classified as MRI incompatible or MRI conditional. The properties of the neurostimulation device and future imaging needs should be taken into consideration when discussing pain management options with patients.
In terms of MRI conditionality, the implanted device featured in this report is restricted to a static magnetic field of 1.5 and 3 T, highest spatial magnetic gradient of 2500 G/cm, and a whole-body average specific absorption rate of 2W/kg to prevent MR-related heating of the lead and thermal injury. Further, the lead must be at least 50 cm from the isocenter of the MRI bore and at least 16 cm from the nearest edge of the radiofrequency coil. Of all the conditions, the distance limitation is the most restricting. If the device is implanted close to a region where future imaging may be required, then alternative options should be considered. There are PNS devices that are designed for 60 day externalized therapies, which can be easily explanted, and permanent SCS implants without distance restrictions for MRIs [27].
Modern PNS devices can be implanted percutaneously under ultrasound. They have a similar side effect profile as SCS including lead migration, lead fracture, infection, pain at insertion site, and discomfort with stimulation. Implementing this treatment modality requires careful consideration of cost, interventional targets, proximity to a growing cancer lesion, risk of complications, and MRI conditionality of the device [13,28]. Our patient's improved pain control and improved quality of life while maintaining independence from ongoing medical treatments provide additional support for use of PNS as a cancer pain treatment option in a palliative setting.
The authors have no sources of funding to declare for this manuscript.
The authors declare the following financial interests/personal relationships which may be considered as potential competing Dr. Christiansen received research grant support from Avanos Medical, Inc. The other authors declare no conflicts of interest.